Citation: Wen-Xuan Shao, Jianyuan Wu, Gaojie Li, Yi-Hao Min, Qiu-Shuang Hu, Yu Liu, Weimin Ci, Bi-Feng Yuan. Quantitative analysis of N⁶-methyladenine at single-base resolution in mitochondrial DNA of hepatocellular carcinoma by deaminase-mediated sequencing[J]. Chinese Chemical Letters, ;2025, 36(10): 110747. doi: 10.1016/j.cclet.2024.110747 shu

Quantitative analysis of N⁶-methyladenine at single-base resolution in mitochondrial DNA of hepatocellular carcinoma by deaminase-mediated sequencing

Wen-Xuan Shao ^{a, b, 1} ,
Jianyuan Wu ^{c, 1} ,
Gaojie Li ^d ,
Yi-Hao Min ^a ,
Qiu-Shuang Hu ^a ,
Yu Liu ^a ,
Weimin Ci ^d ,
Bi-Feng Yuan ^{a, b, e, *,}

a.
Department of Occupational and Environmental Health, School of Public Health, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
b.
Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan 430060, China
c.
Clinical Trial Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
d.
Key Laboratory of Genomics and Precision Medicine, and China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
e.
Hubei Key Laboratory of Biomass Resource Chemistry and Environmental Biotechnology, Wuhan University, Wuhan 430072, China

bfyuan@whu.edu.cn

Received Date: 16 May 2024
Revised Date: 22 October 2024
Accepted Date: 10 December 2024
Available Online: 11 December 2024

Figures(6)

N⁶-methyladenine (6mA) is a prevalent DNA modification and is involved in a wide range of human diseases. Previous studies have indicated that 6mA is enriched in mitochondrial DNA (mtDNA) of mammals. By employing an evolved adenine deaminase, we developed a deaminase-mediated sequencing (DM-seq) method that could achieve genome-wide mapping of 6mA in mammalian mtDNA at single-base resolution. In this study, we used an engineered adenine deaminase, known as TadA8e protein, to map 6mA in mtDNA of hepatocellular carcinoma (HCC) by DM-seq. Through high-throughput sequencing, we identified sixteen 6mA sites in both HCC and adjacent normal tissue mtDNA. The results revealed an increased overall 6mA level in mtDNA associated with HCC. Furthermore, an elevation in 6mA level was observed alongside a decrease in the mRNA levels of the corresponding genes, indicating that increased 6mA level hindered transcription processes related to these genes. These findings demonstrate that 6mA in mtDNA is correlated with HCC and provide evidence supporting the inhibitory effect of elevated 6mA level on subsequent transcriptional activity. This research illuminates the intricate relationship between 6mA modification and transcriptional regulation in the context of HCC, offering valuable insights into the role of 6mA modification in HCC pathogenesis.
- N⁶-methyladenine,
- Deaminase-mediated sequencing,
- Deamination,
- Mitochondrial DNA,
- High-throughput sequencing,
- Hepatocellular carcinoma
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Quantitative analysis of N6-methyladenine at single-base resolution in mitochondrial DNA of hepatocellular carcinoma by deaminase-mediated sequencing

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通讯作者: 陈斌, bchen63@163.com

Quantitative analysis of N⁶-methyladenine at single-base resolution in mitochondrial DNA of hepatocellular carcinoma by deaminase-mediated sequencing